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Select Plant Tannins Induce IL-2R Up-Regulation and Augment Cell Division in T Cells¹

Jeff Holderness^*, Larissa Jackiw^*, Emily Kimmel^*, Hannah Kerns^*, Miranda Radke^*, Jodi F. Hedges^*, Charles Petrie, Patrick McCurley, Pati M. Glee, Aiyappa Palecanda and Mark A. Jutila^2,*

^* Veterinary Molecular Biology, Montana State University, and LigoCyte Pharmaceuticals, Inc., Bozeman, MT 59718

T cells are innate immune cells that participate in host responses against many pathogens and cancers. Recently, phosphoantigen-based drugs, capable of expanding T cells in vivo, entered clinical trials with the goal of enhancing innate immune system functions. Potential shortcomings of these drugs include the induction of nonresponsiveness upon repeated use and the expansion of only the V2 subset of human T cells. V1 T cells, the major tissue subset, are unaffected by phosphoantigen agonists. Using FACS-based assays, we screened primary bovine cells for novel T cell agonists with activities not encompassed by the current treatments in an effort to realize the full therapeutic potential of T cells. We identified T cell agonists derived from the condensed tannin fractions of Uncaria tomentosa (Cat’s Claw) and Malus domestica (apple). Based on superior potency, the apple extract was selected for detailed analyses on human cells. The apple extract was a potent agonist for both human V1 and V2 T cells and NK cells. Additionally, the extract greatly enhanced phosphoantigen-induced T cell expansion. Our analyses suggest that a tannin-based drug may complement the phosphoantigen-based drugs, thereby enhancing the therapeutic potential of T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funding in whole or in part from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Contract HHSN266200400009/N01-AI40009 from the Department of Health and Human Services. This work is also supported by Contract 2000-04446 from the U.S. Department of Agriculture Initiative Future Agriculture and Food Safety, and National Research Initiative. LigoCyte Pharmaceuticals, Inc., together with Montana State University, also holds a National Institutes of Health contract that partially funded this work.

² Address correspondence and reprint requests to Dr. Mark A. Jutila, Veterinary Molecular Biology, Molecular Biosciences Building, Montana State University, 960 Technology Boulevard, Bozeman, MT 59718. E-mail address: uvsmj{at}montana.edu

³ Abbreviations used in this paper: APP, apple polyphenol; PVPP, polyvinylpolypyrrolidone; SEAP, secreted embryonic alkaline phosphatase; LAL, Limulus amebocyte lysate.